Internal-state-dependent control of feeding behavior via hippocampal ghrelin signaling

Abstract

Hunger is an internal state that not only invigorates feeding but also acts as a contextual cue for higher-order control of anticipatory feeding-related behavior. The ventral hippocampus is crucial for differentiating optimal behavior across contexts, but how internal contexts such as hunger influence hippocampal circuitry is unknown. In this study, we investigated the role of the ventral hippocampus during feeding behavior across different states of hunger in mice. We found that activity of a unique subpopulation of neurons that project to the nucleus accumbens (vS-NAc neurons) increased when animals investigated food, and this activity inhibited the transition to begin eating. Increases in the level of the peripheral hunger hormone ghrelin reduced vS-NAc activity during this anticipatory phase of feeding via ghrelin-receptor-dependent increases in postsynaptic inhibition and promoted the initiation of eating. Together, these experiments define a ghrelin-sensitive hippocampal circuit that informs the decision to eat based on internal state.

Keywords: feeding behavior; ghrelin; hippocampus; hunger; internal state; nucleus accumbens; synaptic inhibition.